Aim: We aimed to
report the clinical features related to torsades de pointes (TdP) in
patients with complete AV block (CAVB).

Methods: Patients
with CAVB who were admitted to our instituition between January 2007
and January 2010 were retrospectively evaluated in terms of the
occurence of TdP. The clinical features were compared in patients with
and without TdP using the software of SPSS.

Results:
Sixty-four patients were determined to have CAVB. Three of them had
documented episodes of TdP. All three patients experiencing TdP were
females, whereas 48% of the patients with CAVB were females. The mean
age of patients with TdP was significantly greater than the mean age of
the other patients (85 ±3 vs. 78±7.6, respectively;
p<0.05). In our archives, bradycardia exposure time could be
determined in only 49 patients without TdP. Among them, just 10
patients had been exposed to bradycardia over 48 hours, whereas all of
the 3 patients with TdP had been exposed to bradycardia over 48 hours
(p<0.05). Additionally, in two patients with TdP, we
demonstrated that QT and QTc prolongation increases as the
duration of bradycardia is extended. Furthermore, all patients with TdP
had notched T waves in the ECG on the occurrence day of TdP, whereas
they did not have any notched T wave in their ECG on the admission day.

Conclusion: Among
the patients with CAVB, elderly females are more susceptible to
development of TdP. Delay in institution of physiological heart rate
leads to further QT prolongation and thereby to TdP. Besides QT
prolongation, the finding of T wave notching on ECG may also have a
predictive value for TdP. Keywords: Long
QT, complete AV block, torsades

Introduction

Complete atrioventricular block (CAVB) is potentially lethal and
therefore, an emergent clinical condition. Impulses generated in the
atria can not propagate to the ventricles due to a defect in the
atrioventricular node and/or its adjacent conductive tissue. Temporary
transvenous pacemaker (PM) implantation and transthoracic pacing are
lifesaving treatment methods which could be performed at either bedside
or in laboratory. Decision of PM implantation is particularly
determined by the presence or absence of symptoms directly attributable
to bradycardia. However, CAVB may potentially be associated with lethal
ventricular arrhytmia. CAVB may predispose to acquired long-QT syndrome
(LQTS) and torsade de pointes (TdP). [1, 2] The QT interval is
the electrocardiographic manifestation of ventricular depolarization
and repolarization. Prolonged QT interval and repolarization may cause
early after depolarizations (EADs). EADs that reach the threshold
voltage cause ventricular extrasystoles and tachycardias. In fact,
Dessertenne had described the first TdP in a patient with CAVB.
[3] In terms of patient management, it is essential to determine
patients who are susceptible for the development of torsades de
pointes. In this article, we aimed to evaluate the clinical and
electrocardiographic features foretelling TdP in CAVB.

Methods

All patientsts with CAVB who were admitted to our department between
January 2007 and January 2010 were enrolled for the study. TdP was
defined as a ventricular tachycardia (faster than 150 beats/min and
lasting 5 beats) with a polymorphic configuration. Patients with
CAVB occurring during acute myocardial infarction or vasovagal syncope
were excluded. Data are presented as mean ± SD. The variables
were compared between groups using Chi-square test or Mann–Whitney U
tests, as appropriate. The p values <0.05 were considered
statistically significant.

Result

Sixty-four patients were determined as having CAVB. Three of them had
documented episodes of TdP. Clinical features of the patients with and
without TdP are summarized in Table 1.

Table
1: The Differences Between Patients With and Without TdP

TdP: torsades de point.

Case 1

An 88-years-old female patient with complaints of fatigue and dizziness
was admitted by a primary care physician. Five days later, she had been
transferred to our institution for further evaluation of necessity for
a permanent PM implantation due to CAVB. Her medical history revealed
hypertension. She was on amlodipine for hypertension. Her physical
examination revealed mild systolic murmur at the 4th intercostal space.
Her heart rate was 50 bpm and blood pressure 120/70 mmHg. Her initial
ECG, documented 5 days ago at the time of her first admission, had
demonstrated CAVB with QT and QTc intervals of 420 and 342 ms,
respectively (Figure 1A). The
ECG obtained at her admission to our
institution revealed CAVB with further prolonged QT and QTc intervals
of 604 and 540 ms, respectively (Figure
1B). Additionally, prominent
notches were noticed on the T waves on the second ECG (Figure 1B,
arrows). Her electrolyte levels were in normal ranges. Since her
clinical and hemodynamical status were stable, we did not implant a
temporary PM immediately. A permanent PM implantation was scheduled for
the next morning. During the follow-up in the coronary care unit, ECG
monitoring revealed episodes of TdP (Figure
1C). One of TdP's
degenerated to ventricular fibrillation. She was defibrillated
immediately and a temporary PM was implanted. Temporary ventricular
pacing at a rate of 90 bpm decreased QT interval to 400 ms and no
recurrences of TdP were recorded later on. A DDD-R permanent PM was
implanted on the next day.

Figure 1: A)
12-lead ECG of Case 1 documented 5 days before the development of TdP
showed complete AV block with QT and QTc intevals of 420 msec and 342
ms, respectively. B) ECG on the day of development of torsades
demonstrated further QT prolongation and notched T waves (arrows). C)
Documented episode of TdP during ECG monitorization in coronary care
unit.

Case 2

The second patient was an 85-years-old female with complaints of
dizziness, fatigue and presyncope. Her medical history was remarkable
with coronary artery disease, hypertension, diabetes mellitus and
Alzheimer's diease. She was on multiple drug therapy, including
metformin, ramipril, amlodipine, atorvastatin, doxazosin, clopidogrel,
memantine, paroxetine and mianserine for these diseases. On the
physical examination, her heart rate and blood pressure were 38 bpm and
160/60 mmHg, respectively. ECG revealed CAVB with a heart rate of 38
bpm and narrow QRS. Additionally, QT and QTc intervals on admission
were 510 and 406 ms, respectively. Her electrolyte levels were within
normal ranges. Her all medications having potential to prolong QT
interval were stopped. Since the patient was hemodynamically and
clinically stable, she was followed up in the coronary care unit and
was scheduled for a permanent PM implantation on the next day. 12-lead
ECG obtained on the next day demonstrated further prolongation of the
QT and QTc intervals. QT and QTc intervals were 615 and 471 ms,
respectively. Furthermore, T wave morphology was different compared to
the first ECG. T waves were notched on the second ECG (Figure 2B,
arrows). While waiting for PM implantation, episodes of TdP were
recorded. Transvenous temporary PM was immediately implanted.
Institution of physiological rate via temporary ventricular pacing
decreased QT interval to 410 ms and prevented from recurrences of
torsades.

Figure 2: A) 12-lead
ECG of Case 2 on the admission day demonstrated complete AV block with
QT and QTc intervals of 510 and 406 ms, respectively. B) ECG obtained
on the day of development of torsades demonstrated further QT
prolongation and notched T waves (arrows). C) Documented episode of TdP
during ECG monitorization in coronary care unit.

Case 3

The third patient was a 82-years-old female. She was admitted to our
department with syncope. She was on lisinopril+hydrochlorothiazide,
aspirin and isosorbide mononitrate for hypertension and coronary artery
disease. Three weeks earlier, while she was having complaints of
dizziness and fatigue, she was diagnosed with CAVB. At that time, she
had refused permanent PM implantation. Her physical examination was
unremarkable, except bradycardia with a rate of 47 bpm. The ECG
demonstrated CAVB with QT and QTc intervals of 600 and 531 ms,
respectively (Figure 3A). There
were prominent notches on the T waves,
especially in the leads V3-6 (Figure 3A,
arrows). Her electrolyte
levels were within normal ranges. Because of her new emerged complaint
of syncope, she gave consent for permanent PM implantation. Before
permanent PM implantation, during her stay in the coronary care unit,
episodes of TdP were noticed on ECG monitor (Figure 3B). After
achieving the physiological ventricular rate via temporary PM, episodes
of torsades disappeared.

Figure 3: A)
12-lead ECG of Case 3 three weeks after the diagnosis of complete AV
block when her complaint of syncope begun, showed complete AV block
with QT and QTc intervals of 600 and 531 ms, respectively. B)
Documented episode of TdP during ECG monitorization in catheterization
laboratory.

All of the patients with TdP were females whereas 52% of all patients
with CAVB were males (p<0.05). Mean age of patients with TdP was
significantly greater than the mean age of the patients without TdP
(p<0.05, 85±3 vs 78±7.6, respectively). The most
prominent common clinical feature of the patients with TdP was the
extended exposure to bradycardia, because of the delay in PM
implantation. In patients with TdP, the elapsed times from the
beginning of block to PM implantation were 48 hours, 5 days and 20
days. In our archives, bradycardia exposure time could be determined in
only 49 patients without TdP. Among them, just 10 patients were exposed
to bradycardia for over 48 hours, whereas all 3 patients with TdP were
exposed to bradycardia over 48 hours (p<0.05). As expected, all the
patients with TdP had prolonged QT and QTc intervals on ECG.
Additionally, in two patients with TdP, we demonstrated that QT and QTc
prolongation increases as the duration of bradycardia extends.
Furthermore all the patients with TdP had notched T waves in the ECG on
the occurrence day of TdP.

Discussion

In this retrospective case-control study, it was found that female
gender, advanced age and extended exposure to bradycardia were
foretelling TdP in CAVB patients. Complete AV block causes bradycardic
ventricular remodelling associated with electrophysiological
abnormalities reminiscent of those found in congenital and acquired
LQTS's. [2, 4] These include repolarization delay manifesting
electrocardiographically as QT interval prolongation, and
predisposition to the triggered form of polymorphic ventricular
tachycardia known as TdP.[2] QT interval is measured from the onset of
QRS complex to the termination of T wave.[5] The longest QT intervals
are generally measured in precordial leads V3-V4. The QT interval
normally shortens with tachycardia and extends with bradycardia.
Therefore, a rate corrected QT (QTc) interval should be calculated.
Bazett's formula, in which the longest QT interval divided by the
square root of the RR interval is the gold standart for QTc
calculation. [5] QTc intervals < 440 ms are clearly normal. In all
of our three cases, QTc intervals were abnormally longer than 440 ms on
the occurrence day of TdP (Table 2).

Table
2: Electrocardiographic
Features of the Patients with Torsades de Pointes

NA: not available.

Additionally, CAVB may cause a hyperadrenergic state and ventricular
ectopy, which could result in a long-short phenomenon and TdP, when
timed appropriately.[6, 7] This could potentially happen in a
bradycardic state without significant prolongation of QT interval and
T-wave abnormalities.

According to the ACC/AHA guidelines, pacemaker implantation is a class
I indication for CAVB, associated with symptomatic bradycardia
(including heart failure) or ventricular arrhythmias presumed to be due
to AV block. [8] However, permanent PM implantation is a class IIa
indication for persistent third-degree AV block with an escape rate
greater than 40 bpm in asymptomatic adult patients without
cardiomegaly. In the current AHA/ACC guidelines, QT prolongation is not
referred as an indication for PM implantation in CAVB. It is known that
bradycardia prolongs the QT interval. [9] Studies show that
prolongation of ventricular repolarization which is manifested as QT
prolongation, is a prerequisite for TdP. [2] Furthermore, some patients
with bradycardia have an increased risk for TdP. [9] In their
retrospective case-control study, Topilski and colleagues demonstrated
that some patients have relatively higher risk for TdP in case of
bradycardia. [2] They have demonstrated that female patients with QT
interval>510 ms, QTc interval>400 ms, or Tpeak-Tend>85 ms,
especially if these patients also have type 2 LQTS like notched T
waves (arrows in Figure 1B, 2B, and 3A), are at sufficiently high risk
for developing TdP. In accordance with these findings, all of our three
patients were females and had QT and QTc intervals longer than 510 and
400 ms, respectively (Table 1).
T waves of the cases were also notched
and Tpeak-Tend were longer than 85 ms.

Increased susceptibility to QT prolongation and related TdP is a well
known feature of female gender. Kawasaki et al. have also demonstrated
that female patients with CAVB experience more often TdP than male
patients. [9]

Patients with TdP were older than patients without TdP. Our three cases
were older than 80 years. Although previously not reported, advanced
age may be a factor for the development of TdP in CAVB patients. The
number of our cases is very low when compared with the number of
Topilski's study. They have reported 30 bradicardic patients
complicated by TdP. They have showed that advanced age is not a
predictor for the development of TdP. Our findings may be resulting
from statistical error due to the low number of cases. These data show
that all results need to be verified by studies performed in higher
series of patients.

One of the most prominent common clinical characteristics of our cases
was the delay in achieving the physiological ventricular rate. Vos et
al showed that torsades inducibility is increased as the bradycardia
duration is prolonged. [10] In two of our patients, urgent temporary PM
implantation was not performed at the admission due to the absence of
hemodynamic instability. Because of our laboratory schedule, permanent
PM implantation was planned for the next date available. Supporting the
findings of Vos et al., time dependent QT prolongation and QT interval
morphological changes were documented in two patients. Chronic CAVB
affects ventricular myocyte repolarizing currents of IKr and
IKs via K+
channel downregulation and thereby leads to cellular action potential
prolongation and early after-depolarizations, considered to be a
trigger for TdP. [11] K+ channel
downregulation may be augmented with
time and increased K+ channel downregulation
may be the reason of TdP
in patients with delayed pacemaker implantation. Our understanding is
that bradycardia induced QT prolongation occurs more often in elderly
female patients. Especially, if the duration of bradycardia increases,
QT interval prolongs much more and TdP susceptibility increases.

The other most encountered reason for TdP is drug-induced long QT
syndrome. TdP is most commonly caused by antiarrhytmic medications.
[12] Additionally, dose-dependent QT prolongation has been observed
with psychiatric drugs. [13] In the second case, polytherapy with known
QT prolonging drugs of paroxetine and mianserin may be the other
contributing factors for the development of TdP in addition to CAVB.
[14, 15]

Animal studies have demonstrated that the remodelling process can be
aborted entirely by prompt institution and maintenance of
physiologic-rate via ventricular pacing. [16] In our cases, dramatic QT
interval normalization just after the institution of physiologic
ventricular rate via temporary ventricular pacing was also noted. It is
recommended that pacemakers implanted for bradycardia-induced TdP
should be programmed for a pacing rate of ≥80 bpm, until the QT
interval shortens. [2]

The major limitation of this study is the low number of patients with
TdP. Documenting and reporting episodes of TdP is not easy, because the
frequency of TdP is not so high to report more patients.

In summary, CAVB may cause QT prolongation predisposing TdP. Delay in
PM implantation for the treatment of CAVB may cause further QT
prolongation, and thereby TdP. TdP risk is more increased in female
patients aged 80 years or older and having abnormally prolonged QT
interval and notched T waves on ECG. Monitoring of QT and QTc
intervals and also T wave notching in CAVB may be lifesaving. PM
implantation should not be delayed in this group of patients because of
the increased risk of TdP.

5. Rautaharju PM, Surawicz B,
Gettes LS, Bailey JJ, Childers R, Deal
BJ, et al. AHA/ACCF/HRS recommendations for the standardization and
interpretation of the electrocardiogram: part IV: the ST segment, T and
U waves, and the QT interval: a scientific statement from the American
Heart Association Electrocardiography and Arrhythmias Committee,
Council on Clinical Cardiology; the American College of Cardiology
Foundation; and the Heart Rhythm Society: endorsed by the International
Society for Computerized Electrocardiology. Circulation
2009;119:e241-250.

8. Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA, 3rd, Freedman RA,
Gettes LS, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy
of Cardiac Rhythm Abnormalities: a report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines
(Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update
for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices)
developed in collaboration with the American Association for Thoracic
Surgery and Society of Thoracic Surgeons. Journal of the American
College of Cardiology 2008;51:e1-62.